The specimen consisted of a single mucosa covered polypoid soft tissue mass measuring 1.5 x 1.0 x 0.4 cm. It was formalin fixed and paraffin embedded in toto. Sections revealed a highly vascular well circumscribed tumor. The vascular channels' caliber varied from small to ectatic; few were branching and stag-horn shaped. Majority of vessels were thin walled, few larger ones had thicker walls. There were large intervening areas of hyalinization especially prominent in the perivascular location (Figure 1). The cellular areas were few and showed large cells arranged in sheets and nests. The cells had abundant clear to pale eosinophilic granular cytoplasm (Figure 2). Few showed cytoplasmic vacuoles. Nuclei were centrally located and contained inconspicuous nucleoli in many cells. Mitoses were occasional; there were no areas of necrosis. The tumor was reaching up-to the overlying epithelium, which showed squamous metaplasia and focal ulceration. Although PG was suspected, definite diagnosis was deferred to immunohistochemistry (IHC). Polygonal cells with abundant pale cytoplasm in a highly vascular hyalinized background raised other possibilities- malignant melanoma, metastatic carcinoma, PEComa, chordoma, glomus tumor and epithelioid hemangioendothelioma (EH). The high vascularity and hyalinization warranted exclusion of sinonasal type hemangiopericytoma (SNTHP) and solitary fibrous tumor (SFT).

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Figure 1: Numerous variably sized blood vessels with perivascular hyalinization simulating a vascular neoplasm (H&E; x 200).

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Figure 2: High magnification of the cellular area highlighting the voluminous clear to pale vacuolated cytoplasm in tumor cells (H&E; x 400).

A panel of IHC comprising chromogranin A, neuron specific enolase (NSE), S-100, HMB-45, CD34, CD31, cytokeratin, epithelial membrane antigen (EMA), smooth muscle antigen (SMA) and desmin was performed using appropriate positive and negative controls. Tumor cells strongly expressed chromogranin A and NSE (Figure 3). S-100 expression was scarce and outlined the occasional sustentacular cells and zellballen pattern. CD31 and CD34 expression was limited to endothelial cells (Figure 4). Results of other immuno-stains were negative/ non-contributory. Hence the diagnosis of PG of nose was confirmed.

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Figure 3: Diffuse and strong NSE immuno-expression in tumor cells (NSE; x200).

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Figure 4: CD34 immuno-stain is negative in tumor cells. The endothelial cells acting as an internal control are positive (CD34; x400).

HN PGs differ from abdominal PGs in many aspects^2,3. They are associated with parasympathetic nervous system, while abdominal PGs show evidence of sympathetic activity. Despite ultra-structural evidence of neuroendocrine differentiation in HN PGs, less than 10% produce catecholamines in amounts sufficient to result in headaches, palpitations and perspiration. This is in contrast to almost one-forth of abdominal PGs patients having such symptoms. The frequency of hypertension in HN PGs (42%) is also reported to be lower than abdominal ones (64%)². Endocrine silence of HN PGs usually makes them symptomatic either as space occupying lesion related to their anatomic site or with symptoms secondary to nerve compression such as tinnitus and cranial nerve palsies^2,3. HN PGs are distinctly smaller and less likely to be malignant than their abdominal counterparts^2,5. In a retrospective analysis, Flines et al. did not find any difference in survival between their cohort (mean follow up = 26.4 years) in comparison to the general population. The deaths in their study population were attributed to surgical complications of carotid body tumors⁵. Up-to 30% of HN PGs may be associated with mutations of genes encoding various subunits of succinyl dehydrogenase (SDH) enzyme. Familial PGs are commonly multiple, bilateral and present at an earlier age than sporadic tumors. Molecular tests are indicated only in the setting of family history, previous pheochromocytoma, multiple tumors and age < 40 years⁶.

The nose is an exceptional site of PG. Till date, less than 50 nasal PGs have been described, a testimony to its rarity (1, 3-5, 7-10). Nasal PGs have been reported in a wide age range, 8-72 years^3,7. They often present with nasal obstruction and/or epistaxis as happened in our case^3,4,7. The highly vascular nature of the tumor and trauma attendant to its peculiar location may explain the epistaxis. It may be said that most nasal PGs are non-functional, although occasional reports of Cushing's syndrome secondary to ACTH production are on record⁸. Distinction of de novo nasal PGs arising from nasal mucosa from extension of jugulo-tympanic or vagal tumors is essential to decide surgical aspects and is based on radiologic features⁹. As for HN PGs, most reported nasal tumors have had a benign course, although occasional cases with late recurrence have also been reported¹⁰.

The typical morphology of PGs composed of chief cells and surrounding sustentacular cells may not be obvious in all cases. Extensive secondary changes like hyalinization, ectatic blood vessels, sclerosis and others may render their recognition difficult as happened in our case. NSE expression is almost invariable in PGs. The sustentacular cell network is outlined by S-100 and GFAP immunostains. Demonstration of sustentacular cells may be difficult when tumor cells are present in sheets or large nests, especially in small or fragmented sections¹. Neither atypical histological features nor infiltration are considered indicative of malignancy. Metastasis to organs normally devoid of chromaffin cells remains the only evidence of malignancy^1,10.

Cellular areas of PGs may resemble malignant melanoma, metastatic carcinoma, chordoma, perivascular epithelioid cell tumor (PEComa), glomus tumor and EH, all tumors rare to the nose^11-17. They share cytologic feature of voluminous clear to eosinophilic cytoplasm of the tumor cells. Malignant melanomas usually have prominent nucleoli; they invariably show diffuse positivity for S-100 and HMB-45¹¹. Appropriate clinical setting and expression of epithelial markers will help establishing diagnosis of metastatic carcinoma¹². Physalliferous cells are characteristic of chordoma, but may be few. Chordomas are decorated by cytokeratin, EMA and S-100¹³. In the present case thorough search neither revealed cells with prominent nucleoli nor with spidery cytoplasm. PGs do not stain with epithelial markers or HMB-45 and S-100 staining is limited to sustentacular cells. Radial arrangement of cells around blood vessels and low grade nuclei are seen in PEComa and glomus tumor. Although highly vascular, our case showed large areas of perivascular hyalinization rather than cellularity typical of these tumors. PEComas and glomus tumors typically stain with HMB-45 and SMA respectively^1,14,15. Expression of desmin is variable in both. PGs are typically negative for HMB-45, SMA and desmin. Conversely PEComas and glomus tumors do not express NSE. EH, an angiocentric tumor may show clusters of large cells resembling PG. Intra-cytoplasmic vacuoles often containing erythrocytes indicate its vascular origin. Endothelial cell markers like CD31 and CD34 are expressed consistently in EH^1,16. The cells in the present case did have vacuolated appearing cytoplasm but did not have the typical blistered look of EH; none contained erythrocytes. IHC for CD31 and CD34 outlined the endothelial cells lining the ecstatic vessels; tumor cells did not take the stain.

Highly vascular tumors with staghorn-like branching vessels and prominent hyalinization in this region, albeit rare include SNTHP and SFT^17,18. SNTHP is a low to intermediate grade tumor of perivascular myoid phenotype containing HP like staghorn vessels. Its cells are bland, spindle shaped and arranged in fascicular and/or whorled pattern. Their immuno-phenotype resembles glomus tumor rather than HP. Most react with vimentin (98%), SMA (92%), and factor XIIIa (78%); expression of CD34 is variable¹⁷. The cells in our lesion were polygonal rather than spindle and their immuno-phenotype was typical of neuro-endocrine nature. SFT, a fibroblastic mesenchymal tumor also has prominent HP like branching vasculature. Its cells are generally arranged in fascicular fashion unlike the nesting pattern of polygonal cells of PGs. Its cells stain with CD34, bcl-2 and CD99¹⁸. CD34 stain was consistently absent in tumor cells in our case.

To conclude, we have shared our experience with an unsuspected nasal PG. This rare neoplasm of the nose is likely to be a histologic surprise in the rather common nasal polypectomy specimens. Identification of its typical morphology is essential for correct diagnosis and proper management. Immuno-staining for NSE and chromogranin A is likely to be useful in cases obscured by extensive secondary changes.

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